A new enzyme-linked immunosorbent assay blood test, sclero-smart™, has been released by Gemelli Biotech to aid in the diagnosis of scleroderma.1 The test is the first of its kind to measure anti-vinculin antibody levels in the blood, which have been shown to be elevated among patients with scleroderma and are associated with gastrointestinal complications.

Recent data from the American College of Rheumatology (ACR) show that anti-vinculin antibody levels were higher among patients with systemic sclerosis compared with healthy controls.2 Patients with scleroderma who tested positive for elevated anti-vinculin antibodies also had greater gastrointestinal symptom severity. Given the link between anti-vinculin and intestinal neuropathy, anti-vinculin may be a key marker of gastrointestinal complications among patients with scleroderma.

Anti-vinculin antibodies were also associated with pulmonary hypertension, according to further data from the ACR.3 Therefore, the measurement of these antibodies may help rheumatologists identify patients with scleroderma who are at risk for gastrointestinal or vascular complications.

Mark Pimentel, MD, executive director of the Medically Associated Science and Technology program at Cedars-Sinai Medical Center in Los Angeles, and co-founder of Gemelli Biotech, spoke with Rheumatology Advisor about key future clinical implications of this new technology.

Rheumatology Advisor: How do you envision clinicians incorporating this diagnostic testing into clinical practice?

Dr Pimentel: Knowledge about anti-vinculin antibodies may improve the diagnosis of autoimmune conditions like scleroderma. One of the challenges in diagnosing scleroderma is that up to now, there were no really reliable biomarkers. There are anti-centromere antibodies, anti-Ro/SSA, anti-La/SSB, and anti-RNA-pol-III and other markers, but they are not commonly positive, meaning only about 10% to 30% of [people with] scleroderma may have those markers.   

Anti-vinculin antibodies, in contrast, were found in up to 38% of patients with scleroderma in a recent abstract presented at the ACR 2018 conference. So this is very interesting since it appears that anti-vinculin may be more common than other markers that have been around for a long time.

This testing may really improve the diagnosis of scleroderma. In addition, it is also predictive of symptoms that are related to the gastrointestinal involvement in scleroderma.

We know the vinculin is important for the nerve integrity of the gut. Vinculin is important for keeping the nerves attached or for migrating the nerve cells so that they can adhere to each other. Anti-vinculin antibodies may disturb that adherence, and this may be even the reason why these patients have neuropathies and subsequently myopathies of the gut.

In addition, vinculin is most prevalent in the enteric nervous system and in the skin, where scleroderma is often involved, and manifested in cutaneous tissue with skin thickening. More work needs to be done to understand how these antibodies may be part of the pathophysiology of scleroderma as we continue to unfold this.

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Rheumatology Advisor: How might the human microbiome be linked to other inflammatory conditions?

Dr Pimentel: Currently, we think anti-vinculin antibodies are driven from food poisoning. So, a food poisoning event could have occurred in the past, and then through molecular mimicry an autoantibody is subsequently formed. A patient may also have a genetic predisposition to forming these antibodies.

Then there are later changes in the microbiome. We don’t know if those changes in the microbiome are causing further autoimmune disease, but we think that the initial infection may have triggered autoimmunity.

This is also true for other autoimmune diseases, for example, reactive arthritis (Reiter syndrome) is known to occur after infection. 

Disclosure: Dr Pimentel is co-founder of Gemelli Biotech.

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References

  1. New ELISA blood test from Gemelli Biotech offers important insights to patients with scleroderma and systemic sclerosis [press release]. Los Angeles, California: Gemelli Biotech. https://www.prnewswire.com/news-releases/new-elisa-blood-test-from-gemelli-biotech-offers-important-insights-to-patients-with-scleroderma-and-systemic-sclerosis-300775470.html. Published January 9, 2019. Accessed January 10, 2019.
  2. Suliman YA, Kafaja S, Bagnato G, et al. Anti-vinculin antibodies in systemic sclerosis (SSc): a potential biomarker linking vascular and gastrointestinal system involvement in two phenotypically distinctive SSc groups. Presented at: 2018 ACR/ARHP Annual Meeting; October 19-24, 2018; Chicago, IL. Abstract 2937.
  3. Suliman YA, Kafaja S, Alemam M, et al. Anti-vinculin antibodies: a novel biomarker in systemic sclerosis, and its association with vascular involvement. Presented at: 2016 ACR/ARHP Annual Meeting; November 11-16, 2016; Washington, DC. Abstract 2908.